Synthesis and pharmacological properties of a series of antidopaminergic piperidyl benzamides

Abstract

The synthesis and pharmacological screening for anti‐apomorphine, stomach emptying and local anaesthetic activities of some new piperidylbenzamides is described. One of these, N‐(1′‐benzyl‐4′‐piperidyl)‐2‐methoxy‐4‐amino‐5‐chlorobenzamide (clebopride) is more potent than metoclopramide in tests related to blockade of cerebral dopamine receptors.

Synthesis and Gastrointestinal Prokinetic Activity of Novel Benzamide Derivatives with Amphoteric Side Chains.

“…Amphoteric compounds (19-23) with a straight methylene chain, except for 22, showed more potent gastro-and colon-prokinetic activities than N-methyl analog (61) 11) or 1a, and elongation of the methylene chain led to a decrease in both prokinetic activities. Compound 19 especially exhibited excellent gastro-and colon-prokinetic activities in comparison with 1b.…”

“…The following known intermediates and reference compounds were prepared essentially according to the literature: 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide (metoclopramide 1a), 6) 7) 1-methyl-1H-indazole-3-carbonyl chloride (39d), 8 1H-indole-3-carbonyl chloride (39e), 9) 1-methyl-1H-indole-3-carbonyl chloride (39f), 9) 4-amino-5-chloro-N-(1-methyl-4-piperidyl)-2-methoxybenzamide (61), 11) endo-4-amino-5-chloro-2-methoxy-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)benzamide (62), 7) exo-4-amino-5-chloro-2-methoxy-N-(9-methyl-9-azabicyclo[3.…”

Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer’s disease

“…Activation of different carboxylic acid compounds with 1,1 0 -carbonyldiimidazole (CDI) and subsequent coupling to 1-benzylpiperidin-4-amine or 2-(1-benzylpiperidin-4-yl) ethanamine afforded target compounds w1-23 in good yields [46][47][48] . Structures of all synthesized compounds were characterized by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy (see Supplementary data).…”

Influence of Long-Term Treatment of the Rat with Clebopride on the Morphology of the Mammary Gland

“…Another compound of this class, clebo pride (CBP), was discovered during a system atic investigation of the structure-activity re lationships of a series of benzamides [4], In rats, CBP is a potent antidopaminergic compound which inhibits the circling behav ior associated with unilateral nigro-striatal lesions, antagonizes apomorphine-induced stereotyped behavior and reversal of reserpine akinesia, promotes some degree of cata lepsy and induces ipsilateral circling in apomorphine-treated animals [5,6]. Like other substituted benzamides, CBP also increases dopamine turnover as measured by in creased concentrations of DOPAC in striatal and mesolimbic areas of the rat brain [4], Moreover, since CBP only inhibits dopa mine-stimulated adenylate cyclase at high concentrations [5], but displaces ligands such as (3H)-spiperone from their specific binding sites [7], it appears to be a rather selective antagonist at D2-dopaminergic re ceptors.…”